Although hypothyroidism is associated with many comorbidities, the evidence for its association with all-cause mortality in older adults is limited. To evaluate the association between hypothyroidism and all-cause mortality in older adults. Population-based retrospective cohort study. National Health Insurance Research Database in Taiwan. After 1:10 age/sex/index year matching, 2029 patients aged ≥65 years who received a new diagnosis of hypothyroidism between 2001 and 2011 and 20,290 patients without hypothyroidism or other thyroid diseases were included in the hypothyroidism and nonhypothyroidism cohorts, respectively. All-cause mortality was defined as the primary outcome. Cox proportional hazards regression models were used to calculate the hazard ratios of mortality. To further evaluate the effect of thyroxine replacement therapy (TRT) on mortality, we divided patients with hypothyroidism into two groups: patients who received TRT and those who did not. Hypothyroidism was associated with an increased risk of all-cause mortality [adjusted hazard ratio (aHR), 1.82; 95% CI, 1.68 to 1.98; P < 0.001]. Patients with hypothyroidism who received TRT had a lower risk of mortality than patients who did not receive TRT (aHR, 0.57; 95% CI, 0.49 to 0.66; P < 0.001). Similar results were obtained after further propensity score matching in age-, sex-, and comorbidity-stratified analyses. Hypothyroidism was independently associated with increased all-cause mortality in older adults. In patients with hypothyroidism, TRT was associated with a lower risk of all-cause mortality.